{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:52:58Z","timestamp":1792273978991,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,11,20]],"date-time":"2014-11-20T00:00:00Z","timestamp":1416441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2014,12]]},"abstract":"Aims<\/jats:title>AZD<\/jats:styled-content>7325 is a novel \u03b12,3<\/jats:sub>\u2010subtype\u2010selective partial GABA<\/jats:styled-content>\u2010A<\/jats:styled-content>\u2010receptor modulator. This study investigated the pharmacodynamics of single oral doses of AZD<\/jats:styled-content>7325 2\u2009mg and 10\u2009mg on the central nervous system (CNS<\/jats:styled-content>) compared with placebo and lorazepam 2\u2009mg.<\/jats:p><\/jats:sec>Methods<\/jats:title>This double\u2010blind, randomized, four way crossover study enrolled 16 healthy males and administered two validated CNS<\/jats:styled-content> test batteries to measure drug effects on cognitive, neurophysiologic and psychomotor function and subjective feelings. The pharmacological selectivity of AZD<\/jats:styled-content>7325 was compared with lorazepam by plotting saccadic peak velocity change from baseline (\u0394SPV<\/jats:styled-content>) against body sway (\u0394S<\/jats:styled-content>way) and visual analogue scale for alertness(\u0394VAS<\/jats:styled-content>alertness<\/jats:sub>). This analysis has previously been used to identify \u03b12,3<\/jats:sub>\u2010subtype\u2010selectivity.<\/jats:p><\/jats:sec>Results<\/jats:title>In contrast with the robust impairment caused by lorazepam (all P<\/jats:italic> < 0.05 vs.<\/jats:italic> placebo), neither dose of AZD<\/jats:styled-content>7325 induced statistically significant effects on any pharmacodynamic measurements. Lorazepam\u2010induced SPV\u2010reduction was linearly related to changes in other neurophysiologic biomarkers. In contrast, the slopes of the regression lines were flatter for AZD<\/jats:styled-content>7325, particularly for the \u0394log(S<\/jats:styled-content>way) \u2212<\/jats:bold>\u0394SPV<\/jats:styled-content> relation (estimate slope, AZD7<\/jats:styled-content>325 10\u2009mg vs<\/jats:italic>. lorazepam, difference [95% confidence interval], P<\/jats:italic> value \u22120.00036 vs.<\/jats:italic> \u22120.00206, 0.001704 [0.000639, 0.002768], P<\/jats:italic> = 0.0018) and the \u0394VAS<\/jats:styled-content>alertness<\/jats:sub>\u2212<\/jats:bold>\u0394SPV<\/jats:styled-content> relationship (0.01855 vs.<\/jats:italic> 0.08216, \u22120.06360 [\u22120.1046, \u22120.02257], P<\/jats:italic> = 0.0024). AZD<\/jats:styled-content>7325 10\u2009mg and lorazepam induced different response patterns on VAS<\/jats:styled-content> \u2018feeling high\u2019 and electro\u2010encephalography.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>The characteristic \u0394SPV<\/jats:styled-content>\u2010relative effect profiles of AZD<\/jats:styled-content>7325 vs<\/jats:italic>. lorazepam suggest anxio\u2010selectivity related to \u03b12,3<\/jats:sub>\u2010selective GABAA<\/jats:sub><\/jats:styled-content> agonism. However, exploration of higher doses may be warranted. The paucity of effects on most CNS<\/jats:styled-content>\u2212<\/jats:bold>PD<\/jats:styled-content> parameters also indicates a mitigated side effect pattern, with potentially lower cognitive and neurophysiological side effect burden than non\u2010selective benzodiazepines.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12413","type":"journal-article","created":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T02:09:19Z","timestamp":1399428559000},"page":"1298-1314","source":"Crossref","is-referenced-by-count":45,"title":["The central nervous system effects of the partial GABA<\/scp>\u2010A<\/scp>\u03b12,3<\/sub>\u2010selective receptor modulator AZD7325<\/scp> in comparison with lorazepam in healthy males"],"prefix":"10.1111","volume":"78","author":[{"given":"Xia","family":"Chen","sequence":"first","affiliation":[{"name":"Phase I Unit, Clinical Pharmacology Research Center (CPRC) Peking Union Medical College Hospital Beijing China"},{"name":"Centre for Human Drug Research Leiden The 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